The challenge of identifying efficacious out-patient treatments for depression is amplified by the increasing desire to find interventions that reduce the time to sustained improvement. One potential but underexplored option is triple chronotherapy (TCT). To date, use of TCT has been largely restricted to specialist units or in-patients. Recent research demonstrates that it may be possible to undertake sleep deprivation in out-patient settings, raising the possibility of delivering TCT to broader populations of individuals with depression. Emerging evidence suggests that out-patient TCT is a high-benefit, low-risk intervention but questions remain about how to target TCT and its mechanisms of action. Like traditional antidepressants, TCT probably acts through several pathways, especially the synchronisation of the ‘master clock’. Availability of reliable and valid methods of out-patient measurement of intra-individual circadian rhythmicity and light exposure are rate-limiting steps in the wider dissemination of TCT.

Biological rhythms occur at different levels in the organism. In single cells, the celldivision cycle shows rhythmicity in the way its molecular regulators, the cyclin dependantkinases (CDKs), modulate their activity periodically to ensure a healthy progression. Intissues, cell proliferation is driven by the circadian clock, which modulates theprogression through the cell cycle along the day. The circadian clock shows endogenousrhythmicity through a robust network of transcription-translation feedback loops thatcreate sustained oscillations. Rhythmicity is preserved in cell populations by thecoordination of the clocks among cells, through rhythmic synchronization signals. Here wediscuss mechanisms for generating rhythmic activities in cell populations by reviewingsome of the mathematical models that deal with them. We discuss the implication ofbiological rhythms for tissue growth and the possible application to chronomodulatedcancer treatments.

We study the growth rate of a cell population that follows anage-structured PDE with time-periodic coefficients. Our motivationcomes from the comparison between experimental tumor growth curvesin mice endowed with intact or disrupted circadian clocks,known to exert their influence on the cell division cycle.We compare the growth rate of the model controlled by a time-periodiccontrol on its coefficients with the growth rate of stationarymodels of the same nature, but with averaged coefficients. We firstly derive a delay differential equation which allows us to proveseveral inequalities and equalities on the growth rates. We alsodiscuss about the necessity to take into account the structure ofthe cell division cycle for chronotherapy modeling. Numerical simulationsillustrate the results.